ATP activates bestrophin ion channels through direct interaction.

ABSTRACT: Human Bestrophin1 (hBest1) is a Ca²⁺-activated Cl^- channel in retinal pigment epithelium (RPE) essential for retina physiology, and its mutation results in retinal degenerative diseases that have no available treatments. Here, we discover that hBest1's channel activity in human RPE is significantly enhanced by adenosine triphosphate (ATP) in a dose-dependent manner. We further demonstrate a direct interaction between ATP and bestrophins, and map the ATP-binding motif on hBest1 to an intracellular loop adjacent to the channel activation gate. Importantly, a disease-causing mutation of hBest1 located within the ATP-binding motif, p.I201T, diminishes ATP-dependent activation of the channel in patient-derived RPE, while the corresponding mutants in bestrophin homologs dis

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6081419 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature